288 research outputs found
SiO excitation from dense shocks in the earliest stages of massive star formation
Molecular outflows are a direct consequence of accretion, and therefore they
represent one of the best tracers of accretion processes in the still poorly
understood early phases of high-mass star formation. Previous studies suggested
that the SiO abundance decreases with the evolution of a massive young stellar
object probably because of a decay of jet activity, as witnessed in low-mass
star-forming regions. We investigate the SiO excitation conditions and its
abundance in outflows from a sample of massive young stellar objects through
observations of the SiO(8-7) and CO(4-3) lines with the APEX telescope. Through
a non-LTE analysis, we find that the excitation conditions of SiO increase with
the velocity of the emitting gas. We also compute the SiO abundance through the
SiO and CO integrated intensities at high velocities. For the sources in our
sample we find no significant variation of the SiO abundance with evolution for
a bolometric luminosity-to-mass ratio of between 4 and 50 . We
also find a weak increase of the SiO(8-7) luminosity with the bolometric
luminosity-to-mass ratio. We speculate that this might be explained with an
increase of density in the gas traced by SiO. We find that the densities
constrained by the SiO observations require the use of shock models that
include grain-grain processing. For the first time, such models are compared
and found to be compatible with SiO observations. A pre-shock density of
cm is globally inferred from these comparisons. Shocks with a
velocity higher than 25 km s are invoked for the objects in our sample
where the SiO is observed with a corresponding velocity dispersion. Our
comparison of shock models with observations suggests that sputtering of
silicon-bearing material (corresponding to less than 10% of the total silicon
abundance) from the grain mantles is occurring.Comment: Accepted for publication by A&
Star Forming Dense Cloud Cores in the TeV {\gamma}-ray SNR RX J1713.7-3946
RX J1713.7-3946 is one of the TeV {\gamma}-ray supernova remnants (SNRs)
emitting synchrotron X rays. The SNR is associated with molecular gas located
at ~1 kpc. We made new molecular observations toward the dense cloud cores,
peaks A, C and D, in the SNR in the 12CO(J=2-1) and 13CO(J=2-1) transitions at
angular resolution of 90". The most intense core in 13CO, peak C, was also
mapped in the 12CO(J=4-3) transition at angular resolution of 38". Peak C shows
strong signs of active star formation including bipolar outflow and a
far-infrared protostellar source and has a steep gradient with a
r^{-2.20.4} variation in the average density within radius r. Peak C and
the other dense cloud cores are rim-brightened in synchrotron X rays,
suggesting that the dense cloud cores are embedded within or on the outer
boundary of the SNR shell. This confirms the earlier suggestion that the X rays
are physically associated with the molecular gas (Fukui et al. 2003). We
present a scenario where the densest molecular core, peak C, survived against
the blast wave and is now embedded within the SNR. Numerical simulations of the
shock-cloud interaction indicate that a dense clump can indeed survive shock
erosion, since shock propagation speed is stalled in the dense clump.
Additionally, the shock-cloud interaction induces turbulence and magnetic field
amplification around the dense clump that may facilitate particle acceleration
in the lower-density inter-clump space leading to the enhanced synchrotron X
rays around dense cores.Comment: 22 pages, 7 figures, to accepted in The Astrophysical Journal. A full
color version with higher resolution figures is available at
http://www.a.phys.nagoya-u.ac.jp/~sano/ApJ10/ms_sano.pd
Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging
IntroductionDementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI).MethodsAtlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimerβs disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification).ResultsThe binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration.DiscussionResults suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimerβs disease
Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.
Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells
A mass spectrometry guided approach for the identification of novel vaccine candidates in gram-negative pathogens
Vaccination is the most effective method to prevent infectious diseases. However, approaches to identify novel vaccine candidates are commonly laborious and protracted. While surface proteins are suitable vaccine candidates and can elicit antibacterial antibody responses, systematic approaches to define surfomes from gram-negatives have rarely been successful. Here we developed a combined discovery-driven mass spectrometry and computational strategy to identify bacterial vaccine candidates and validate their immunogenicity using a highly prevalent gram-negative pathogen, Helicobacter pylori, as a model organism. We efficiently isolated surface antigens by enzymatic cleavage, with a design of experiment based strategy to experimentally dissect cell surface-exposed from cytosolic proteins. From a total of 1,153 quantified bacterial proteins, we thereby identified 72 surface exposed antigens and further prioritized candidates by computational homology inference within and across species. We next tested candidate-specific immune responses. All candidates were recognized in sera from infected patients, and readily induced antibody responses after vaccination of mice. The candidate jhp_0775 induced specific B and T cell responses and significantly reduced colonization levels in mouse therapeutic vaccination studies. In infected humans, we further show that jhp_0775 is immunogenic and activates IFN gamma secretion from peripheral CD4(+) and CD8(+) T cells. Our strategy provides a generic preclinical screening, selection and validation process for novel vaccine candidates against gram-negative bacteria, which could be employed to other gram-negative pathogens
Radio emission from Supernova Remnants
The explosion of a supernova releases almost instantaneously about 10^51 ergs
of mechanic energy, changing irreversibly the physical and chemical properties
of large regions in the galaxies. The stellar ejecta, the nebula resulting from
the powerful shock waves, and sometimes a compact stellar remnant, constitute a
supernova remnant (SNR). They can radiate their energy across the whole
electromagnetic spectrum, but the great majority are radio sources. Almost 70
years after the first detection of radio emission coming from a SNR, great
progress has been achieved in the comprehension of their physical
characteristics and evolution. We review the present knowledge of different
aspects of radio remnants, focusing on sources of the Milky Way and the
Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief
overview of theoretical background, analyze morphology and polarization
properties, and review and critical discuss different methods applied to
determine the radio spectrum and distances. The consequences of the interaction
between the SNR shocks and the surrounding medium are examined, including the
question of whether SNRs can trigger the formation of new stars. Cases of
multispectral comparison are presented. A section is devoted to reviewing
recent results of radio SNRs in the Magellanic Clouds, with particular emphasis
on the radio properties of SN 1987A, an ideal laboratory to investigate
dynamical evolution of an SNR in near real time. The review concludes with a
summary of issues on radio SNRs that deserve further study, and analyzing the
prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure
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JUPITER-II Molten Salt Flibe Research: An Update On Tritium, Mobilization and Redox Chemistry Experiments
The second Japan/US Program on Irradiation Tests for Fusion Research (JUPITER-II) began on April 1, 2001. Part of the collaborative research centers on studies of the molten salt 2LiF2βBeF2 (also known as Flibe) for fusion applications. Flibe has been proposed as a self-cooled breeder in both magnetic and inertial fusion power plant designs over the last 25 years. The key feasibility issues associated with the use of Flibe are the corrosion of structural material by the molten salt, tritium behavior and control in the molten salt blanket system, and safe handling practices and releases from Flibe during an accidental spill. These issues are all being addressed under the JUPITER-II program at the Idaho National Laboratory in the Safety and Tritium Applied Research (STAR) facility. In this paper, we review the program to date in the area of tritium/deuterium behavior, Flibe mobilization under accident conditions and testing of Be as a redox agent to control corrosion. Future activities planned through the end of the collaboration are also presented
A CI-Independent Form of Replicative Inhibition: Turn Off of Early Replication of Bacteriophage Lambda
Several earlier studies have described an unusual exclusion phenotype exhibited by cells with plasmids carrying a portion of the replication region of phage lambda. Cells exhibiting this inhibition phenotype (IP) prevent the plating of homo-immune and hybrid hetero-immune lambdoid phages. We have attempted to define aspects of IP, and show that it is directed to repΞ» phages. IP was observed in cells with plasmids containing a Ξ» DNA fragment including oop, encoding a short OOP micro RNA, and part of the lambda origin of replication, oriΞ», defined by iteron sequences ITN1-4 and an adjacent high AT-rich sequence. Transcription of the intact oop sequence from its promoter, pO is required for IP, as are iterons ITN3β4, but not the high AT-rich portion of oriΞ». The results suggest that IP silencing is directed to theta mode replication initiation from an infecting repΞ» genome, or an induced repΞ» prophage. Phage mutations suppressing IP, i.e., Sip, map within, or adjacent to cro or in O, or both. Our results for plasmid based IP suggest the hypothesis that there is a natural mechanism for silencing early theta-mode replication initiation, i.e. the buildup of Ξ» genomes with oop+
oriΞ»+ sequence
The Pyrimidine Nucleotide Biosynthetic Pathway Modulates Production of Biofilm Determinants in Escherichia coli
Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions
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